Bovine babesiosis is an intraerythrocytic protozoan disease of cattle caused by Babesia bigemina, Babesia bovis, Babesia major, Babesia divergens, and Babesia jakirnovi. These parasites have antigenie similarities and differences that may have important functional roles in the induction of protective immunity and antibody-based diagnosis. Also, B. boris isolates, including the current Australian vaccine strain, are now known to consist of subpopulations that vary antigenically, in virulence, and in abundance within an isolate (Cowman, A. F., P. Timms, and D. J. Kemp [1984]Mol. Biochem. Parasitol. 11:91-103; Gill, A. C., A. F. Cowman, N. P. Stewart, D. J. Kemp, and P. Timms [1987]Exp. Parasitol. 63:180-188). Other mammals may also be subject to infection by species of Babesia. The disease is enzootic to tropical and subtropical climates where it poses severe constraints on livestock production. The risk of the disease and losses caused by it restrict movement of cattle to and from such enzootic regions. This restricted movement results in the loss of opportunities to upgrade local herds by importation of genetically superior breeds susceptible to the disease. Though some degree of immunity has been shown to develop following natural infection (Hall, W. J. K. et al. [1968] Aust. Vet. J. 44:259-264; Mahoney, D. F. et al. [1973] Annals Trop. Med. and Parasit. 67:197-203), significant losses of cattle, meat, and milk production still result from babesiosis induced by Babesia bigemina.
The infective form of Babesia bigemina is the sporozoite which is found in the salivary gland of infected Boophilus microplus and possibly other species of Boophilus ticks. After being introduced into the tissues of the bovine host by the bite of a tick, the sporozoites enter red blood cells (erythrocytes) of the host animal. The sporozoites multiply and develop into merozoites within the erythrocytes. Infection initiates a cycle of host erythrocyte invasion and lysis that results in the clinical disease, babesiosis, which can often result in the death of the host. Recovery from acute babesiosis is associated with immunological response including development of long lasting protective immunity against subsequent challenge.
Despite many years of research relating to babesiosis, effective practical vaccines or other immunoprophylaxes against Babesia bigemina induced babesiosis are not available to the herdsman. The most common vaccination practice in use today is premunition, which is the inoculation of susceptible animals with blood infected with parasites which have been rendered less virulent (Callow, L. L. [1977] "Immunity to Blood Parasites of Animals and Man," In Vaccination Against Bovine Babesiosis, Plenum Press, NY, pp. 121; Dalgliesh, R. J. et al. [1981] Aust. Vet. J. 57:8-11). Although premunition provides good immunity against both homologous and heterologous strain challenge, it has a number of drawbacks, including: (a) induction of a carrier state which perpetuates the protozoan life cycle in the environment; (b) variation in the vaccine virulence which results in death, abortion, or clinical disease in some vaccinates; (c) contamination of the inoculant with other blood-borne infectious agents such as bovine leukosis virus, bluetongue virus, anaplasma, and theileria; (d) cumbersome and expensive production, storage, and transport procedures which render vaccination impractical in many parts of the world; and (e) contamination of the vaccinates with host erythrocytes. Various experimental vaccines using inactivated Babesia parasites only provide partial protection against homologous strain challenge and poor protection against heterologous strain challenge.
Some specific immunogens of Babesia bovis merozoites have been identified and characterized (Smith, R. D., M. A. James, M. Ristic, M. Aikawa, and C. A. Vega Y Murgula [1981] Science 212:335-338; Wright, I. G., M. White, P. O. Tracey-Patte, R. A. Donaldson, B. V. Goodger, D. J. Waltisbuhl, and D. F. Mahoney [1983] Infect. Immun. 41:244-250; Wright, I. G., G. B. Mirre, K. Rode-Bramanis, M. Chamberlain, B. V. Goodger, and D. J. Mahoney [1985] Infect. Immun. 48:109-113; Commins, M. A., B. V. Goodger, and I. G. Wright [1985] Int. J. Parasitol. 15:491-495; Waltisbuhl, D. J., B. V. Goodger, I. G. Wright, G. B. Mirre, and M. A. Commins [1987] Parasitol Res. 73:319-323; Montenegro-James et al. [1987] Parasitol. Res. 74:142-150; Goodger et al. [Int. J. Parasitol. 17:935-940; Goodger et al. Int. J. Parasitol. 15:175-179; Goff W. L., W. C. Davis, G. H. Palmer, T. F. McElwain, W. C. Johnson, J. F. Bailey, T. C. McGuire [1988] Infect. Immun. 56:2363-2368) as well as the merozoite immunogens of Babesia bigemina (McElwain, T. F., L. F. Perryman, W. C. Davis, and T. C. McGuire [1987] J. Immunol. 138(7):2298-2304; Callow, L. L. et al. [1974] Aust. Vet. J. 50:12-15; Kuttler, K. L. et al. [1980]Am. J. Vet. Res. 41:536-538; Montenegro-James et al. [1987] Parasitol. Res. 74:142-150; Figueroa et al. [1990]Parasitology 100(pt. 2):161-175; Figueroa and Buening [1991] J. Clin. Micro. 29:997-1003). However, in only one instance (Smith et al., 1981) were antigens which provided protection against infection determined to be surface-exposed on merozoites as opposed to cytoplasmic in location.
Current vaccine strategies include the use of attenuated live Babesia bovis parasites (Callow et al. [1979] Int. J. Parasitol. 9:333-338) and various inactivated preparations (Montenegro-James, S., M. Toro Benitez, E. Leon, R. Lopez, and M. Ristic [1987] Parasitol. Res. 74:142-150; Smith et al., 1981; U.S. Pat. No. 4,762,711 issued to Buening et al.; Kuttler, K. L., M. G. Levy, M. A. James, M. Ristic [1982] Am. J. Vet. Res. 43(2):281-284; Kuttler, K. L. et al. [1983] Am. J. Vet. Res. 44:1456-1459). Protection of cattle against B. bovis has been compared using commercial B. bovis vaccines, live parasites, or non-living supernatant antigens (Timms, P. et al. [1983] Aust. Vet. J. 60:75-77). The attenuated vaccine provides the best protection against challenge with both homologous and heterologous strains, although there are a number of serious disadvantages, including a short shelf-life, variation in virulence, contamination with host erythrocyte stroma, and perpetuation of the life cycle by creation of a carrier state. Inactivated vaccines induce protection against challenge with homologous strains; however, only partial protection occurs against challenge with heterologous strains. In addition, with the exception of Montenegro-James et al., these vaccine strategies have been directed solely to protection against babesiosis induced from B. bovis strains.
Animals that survive natural field infection or that recover from infection with an attenuated vaccine strain are protected against clinical disease. However, premunization in this manner is expensive, impractical in developing countries that lack the necessary infrastructure, and a potential mode of transmission for other blood-borne diseases.
There remains a need to overcome the known disadvantages of prior art vaccines by developing vaccines and methods for preventing or minimizing the pathological effects of Babesia bigemina induced babesiosis.